PhD sommer

Title

Background

The thesis was submitted during the end of 2012 and defended at 14th January 2013 at Bielefeld University. It was supervised by Prof. Dr. Ralf Hofestädt and co-supervised by Prof. Dr. Karl-Josef Dietz and Prof. Dr. Falk Schreiber. The PDF of the thesis is freely available via the link below.

Abstract

The modeling of cells is an important application area of Systems Biology. In the context of this work, three cytological levels are defined: the mesoscopic, the molecular and the functional level. A number of related approaches which are quite diverse will be introduced during this work which can be categorized into these disciplines. But none of these approaches covers all areas. In this work, the combination of all three aforementioned cytological levels is presented, realized by the CELLmicrocosmos project, combining and extending different Bioinformatics-related methods. The mesoscopic level is covered by CellEditor which is a simple tool to generate eukaryotic or prokaryotic cell models. These are based on cell components represented by three-dimensional shapes. Different methods to generate these shapes are discussed by using partly external tools such as Amira, 3ds Max and/or Blender; abstract, interpretative, 3D-microscopy-based and molecular-structure-based cell component modeling. To communicate with these tools, CellEditor provides import as well as export capabilities based on the VRML97 format. In addition, different cytological coloring methods are discussed which can be applied to the cell models. MembraneEditor operates at the molecular level. This tool solves heterogeneous Membrane Packing Problems by distributing lipids on rectangular areas using collision detection. It provides fast and intuitive methods supporting a wide range of different application areas based on the PDB format. Moreover, a plugin interface enables the use of custom algorithms. In the context of this work, a high-density-generating lipid packing algorithm is evaluated; The Wanderer. The semi-automatic integration of proteins into the membrane is enabled by using data from the OPM and PDBTM database. Contrasting with the aforementioned structural levels, the third level covers the functional aspects of the cell. Here, protein-related networks or data sets can be imported and mapped into the previously generated cell models using the PathwayIntegration. For this purpose, data integration methods are applied, represented by the data warehouse DAWIS-M.D. which includes a number of established databases. This information is enriched by the text-mining data acquired from the ANDCell database. The localization of proteins is supported by different tools like the interactive Localization Table and the Localization Charts. The correlation of partly multi-layered cell components with protein-related networks is covered by the Network Mapping Problem. A special implementation of the ISOM layout is used for this purpose. Finally, a first approach to combine all these interrelated levels is represented; CellExplorer which integrates CellEditor as well as PathwayIntegration and imports structures generated with MembraneEditor. For this purpose, the shape-based cell components can be correlated with networks as well as molecular membrane structures using Membrane Mapping. It is shown that the tools discussed here can be applied to scientific as well as educational tasks: educational cell visualization, initial membrane modeling for molecular simulations, analysis of interrelated protein sets, cytological disease mapping. These are supported by the user-friendly combination of Java, Java 3D and Web Start technology. In the last part of this thesis the future of Integrative Cell Modeling is discussed. While the approaches discussed here represent basically three-dimensional snapshots of the cell, prospective approaches have to be extended into the fourth dimension; time.

mediengestaltung

Mediengestaltung is a study which is offered as a cooperation between the University of Bielefeld and the Fachhochschule Gestaltung Bielefeld. It has been one of the first bachelor studies and was initialized in the year 2000.

Right from the beginning, the concept of the study has been a mixture of informatic and design. (A part of this intention is of course also a part of the CELLmicrocosmos project.) The students have to handle a lot of math and informatic courses as well as typographic, design and photo courses. Today it is in fashion for universities to offer interdisciplinary studies, Mediengestaltung has been one of the first.

In 2005 the name and some details of the study has been changed, but the intention stays the same: It is now called Medieninformatik und Gestaltung. During the last years, the amount of the bachelor thesis has been reduced. In 2004, when the CELLmicrocosmos project has been finished, it often has been ca. 3/4 of a diploma, today it is often only a small project like the creation of a website or a corporate identity. In addtion the study now lasts only 6 semesters, while the old one lasted 7. This is a concession to the compatibility to the amount of other bachelor studies and to increase the importance of a more science-oriented master study.

If you want to find out more about the Medieninformatik und Gestaltung study and its wide spectrum of courses, please visit the site of the University of Bielefeld.

diploma sebastian schneider

Introduction

The goal of the diploma thesis “Entwicklung einer Schnittstelle zur Integration membranberechnender Algorithmen in den CELLmicrocosmos2.1” was to develop an Interface for the CELLmicrocosmos 2.1 program that allows to embed algorithms for membrane-calculation. With this interface it should be possible to integrate self developed algorithms using methods like Molecular Dynamics, Monte-Carlo or whichever serve the demands.

History

In former versions of the CELLmicrocosmos 2 program (Cm2 / Cm2.1) there were predefined ways to calculate the membrane. They had been accurate for generating large membranes with high speed but ignored scientific methods.

Another insufficiency was that this methods where proper for some aims but dissatisfying for other interests. Coming to the conclusion that there is no possibility to create a method that is on the one hand fast and on the other hand adequate to all interests the idea was formed that a plug-in structure could help out of this predicament.

diploma prolog

Therefore some subgoals had to be finalized. One was the internal and graphical representation of the molecules. The former two dimensional representation was raised to a three dimensional using Java3D. Resultant three dimensional calculations could be realized. Another point was the unclear structure of the molecules. They contain a lot of information unnecessary for the calculation of membranes. Wrapping classes hide these informations and present only relevant data.

diploma

The main part of the diploma was the development of the interface. This is defined by a protocol, a plug-in manager and a package of methods. The protocol defines how algorithm should be structured so that they can be included into the CELLmicrocosmos 2.1 program.

The plug-in manager allows to load and run algorithms in the CELLmicrocosmos2.1 program. A last point are the methods which handle the consistency between internal and graphical representation. Also a lot of basic methods are included helping to create and delete molecules, detect collisions, measure distances, etc.

Another part of the diploma was the creation of membrane-calculating algorithms. Therefore three algorithms had been written which are basically included into the Cm 2.1 program. One very fast but without dynamic, one with more dynamic but still fast and one more complex but costly in terms of time algorithm based on a Simulated-Annealing Algorithm resemble Monte-Carlo probability methods.